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Blood, 15 September 2001, Vol. 98, No. 6, pp. 1708-1713
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Phase 1 study of polyethylene glycol formulation of interferon
 -2B (Schering 54031) in Philadelphia chromosome-positive chronic
myelogenous leukemia
Moshe Talpaz,
Susan O'Brien,
Esther Rose,
Samir Gupta,
Jianqin Shan,
Jorge Cortes,
Francis J. Giles,
Stefan Faderl, and
Hagop M. Kantarjian
From the Departments of Bioimmunotherapy and Leukemia,
M. D. Anderson Cancer Center, Houston, TX, and Schering-Plough
Research Institute, Kenilworth, NJ.
Interferon  (IFN-) therapy improves prognosis in Philadelphia
chromosome (Ph)-positive chronic myelogenous leukemia (CML). Polyethylene glycol (PEG) attached to IFN- prolongs its half-life and may offer better therapy. The aims of this phase 1 study were to
define the maximal tolerated dose (MTD), dose-limiting toxicities (DLTs), and response with PEG IFN--2b. Twenty-seven adults with Ph+ CML in chronic or accelerated phases, in whom IFN-
treatment had failed, were studied. Patients had hematologic (9 patients) or cytogenetic resistance (12 patients) or intolerance to
IFN- (6 patients). PEG IFN--2b was given as a weekly subcutaneous injection starting at 0.75 µg/kg weekly and escalating to 1.5, 3, 4.5, 6, 7.5, and 9.0 µg/kg. The MTD was defined at 7.5 to 9 µg/kg;
DLT included severe fatigue, neurotoxicity, liver function abnormalities, and myelosuppression. Longer administration of PEG
IFN--2b resulted in chronic side effects not observed earlier, which
defined the MTD and DLT. The proposed phase 2 dose of PEG IFN--2b
was 6 µg/kg weekly. Among 19 patients with active disease, 7 (37%)
achieved complete hematologic response (CHR); 2 (11%) had a
cytogenetic response (complete). Among 8 patients treated in CHR, 7 (87%) improved cytogenetic response to complete (4 patients) or
partial (3 patients). All 6 patients intolerant to IFN- tolerated PEG IFN--2b; 4 improved their cytogenetic response. The results show
that PEG IFN--2b is easier to deliver (once weekly), better tolerated, and perhaps more effective than IFN-.
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